1. Technical Field of the Invention
The present invention relates to a magnetic resonance apparatus for acquiring pieces of chemical and physical information in relation to various types of substances by making use of a magnetic resonance phenomenon, and in particular, to magnetic resonance spectroscopy or magnetic resonance spectroscopic imaging based on a technique known as multiple-quantum-coherence transfer.
2. Related Art
A magnetic resonance apparatus has been widely used in applications such as chemical analysis and medical diagnosis in order to acquire chemical and physical information about various substances. Some representative techniques include magnetic resonance imaging (MRI; hereafter referred to as xe2x80x9cMRIxe2x80x9d), magnetic resonance spectroscopy (MRS; hereafter referred to as xe2x80x9cMRSxe2x80x9d), and magnetic resonance spectroscopic imaging (MRSI; hereafter referred to as xe2x80x9cMRSIxe2x80x9d).
The MRI has been mainly used in the medical field, in which a distribution of water can be imaged based on information about relaxation time or others of magnetic spins present in an organism. Thus, contour information and/or functional information of an object to be examined can be obtained in a non-invasive manner. For this reason, MRI systems have become indispensable modalities for the clinical purpose.
On the other hand, an MRS system is able to provide magnetic resonance spectroscopy of a substance, while an MRSI system has the capability of providing a spectroscopic distribution. Both systems detect a magnetic resonance signal of 1H, 13C, 31P or others of a metabolite, so that they provide non-invasively information about metabolism in an object to be examined.
For magnetic resonance spectroscopy and magnetic resonance spectroscopic imaging, a difference between magnetic environments of 1H or others (, which results from a difference between molecular structures of metabolites), that is, a difference between chimerical shifts causes a slight difference between their resonance frequencies. Such frequency differences produce separated peaks of resonance frequency curves of metabolites shown along the frequency axis. For example, xe2x80x9c1H MRSxe2x80x9d for the brain provides the peaks of various metabolites including N-acetyl-aspartate (NAA), creatine (Cr), choline (Cho), xcex3-aminobutyric acid (GABA). Because these metabolites are substances produced due to chemical changes, that is, changes in the metabolism in the brain, it is expected that detecting the peaks enables diagnosis of metabolic errors.
As representatives for practical data acquisition sequences for the foregoing MRS and MRSI, there have been known various techniques including a PRESS (point resolved spectroscopy) technique and a STEAM (stimulated echo acquisition mode) technique.
FIG. 1 shows a PRESS sequence used as the data acquisition sequence for MRS, while FIG. 2 a STEAM sequence used as the data acquisition sequence for MRSI. In both the sequences, the spatial three axes are depicted by references i, j and k, in which the three axes can arbitrarily be assigned to the physical x-, y- and z-axes.
In these sequences, a pulse for suppressing a water signal, which is for example a CHESS pulse, is first applied, thus the water signal being saturated in a pseudo manner. Localized excitation pulses consisting of appropriately combined radio-frequency magnetic pulses (RF pulses) and gradient pulses are then sequentially applied in the three-axis directions. In response to those applications, echo signals arising from a three-dimensional localized region are acquired. (Of the localized excitation pulses, the radio-frequency magnetic pulses are called slice selection pulses and the gradient pulses are called as slice gradient pulses, respectively, when necessary.) The PRESS sequence enables acquisition of spin echo signals, whereas the STEAM sequence enables acquisition of stimulated echo signals. Reconstructing the acquired signals provides a frequency spectrum at the localized region.
The PRESS and STEAM techniques are preferable for detecting peaks of NAA, Cr, Cho and others in spectroscopy. For instance, as shown in FIG. 3A, there are several hydrogen nuclei 1H in the NAA molecule. 1H-MRS is normally directed to the detection of 1H present in CH3, which is a target to be detected. Carbon nuclei present in the NAA are numbered as illustrated in FIG. 3A, so the above CH3 belongs to NAA C6. A hydrogen nucleus 1H coupled with the carbon nuclei C6 is referred to as an NAA-6. The NAA-6 has a peak at a 1H chemical shift of 2.02 ppm, and the peak is observable by the PRESS sequence or STEAM sequence.
In contrast, the other hydrogen nuclei 1H of NAA, i.e., NAA-2 and NAA-3 are unobservable, because the NAA-2 and NAA-3 are subjected to a homonuclear spin-spin coupling (called JHH coupling) between their nuclei 1H. The magnitude of this spin-spin coupling is expressed by a spin-spin coupling constant JHH (normally expressed with the unit xe2x80x9cHzxe2x80x9d). The NAA-2 is individually coupled with two hydrogen nuclei 1H of the NAA-3. As a result, the NAA-2 shows four split peaks, thus reducing the intensity of a signal. However, in the case of the NAA-6, it is magnetically equivalent to three hydrogen nuclei 1H and there is no nucleus 1H around the NAA-6, thus having no JHH coupling. Hence the peak of a higher intensity is provided, thus being observable. As described, when the NAA in an organism is observed, it is enough to detect the NAA-6. The fact that the NAA-2 and NAA-3 are difficult to observe has not become a problem, so that the foregoing PRESS sequence and others can be used to observe the NAA.
On the other hand, in the xcex3-aminobutyric acid (GABA) that plays a significant role as a nerve transmission substance in the suppression system in the human brain, all the hydrogen nuclei 1H are connected to each other through the homonuclear spin-spin coupling. The GABA is one of the metabolites that are difficult to observe under the PRESS or STEAM sequence. The GABA has hydrogen nuclei 1H belonging to GABA-2, -3 and -4, as shown by the molecular formula in FIG. 3B, all of which are JHH-coupled to each other. An abundance of the GABA is no less than about 1 mM, which is equivalent to about a tenth of that of NAA or Cr. This is one reason that makes it difficult to observe the GABA. To overcome this difficulty, several methods of editing a GABA peak, that is, GABA observation that makes use of the homonuclear spin-spin coupling, have been proposed.
One method is a difference spectrum method based on an inverted GABA-3. (Refer to xe2x80x9cD. L. Rothmanetal., Proc. Natl. Acad. Sci. USA, vol.90, pp.5662-5666, 1993.xe2x80x9d) In the GABA, a chemical shift of GABA-2 is 2.30 ppm, that of GABA-3 is 1.91 ppm, and that of GABA-4 is 3.01 ppm, and JHH is 7.3 Hz. Hence, in the case of the static field is 1.5 T in strength, which can be obtained by ordinary used clinical MR systems, a frequency difference xcex94xcfx89 between the GABA-2 and GABA-3 is xcex94xcfx89=24.9 Hz and xcex94xcfx89/JHH=3.4. Between the GABA-3 and GABA-4, xcex94xcfx89=70.2 Hz and xcex94xcfx89/JHH=9.6. Accordingly, the GABA-2 is strongly coupled to the GABA-3, while the GABA-3 is coupled to the GABA-4 with an intervening force slightly weaker than that between the GABA-2 and GABA-3. Thus, the difference spectrum method makes use of the coupling between the GABA-3 and GABA-4 in order to observe the GABA-4.
Pulse sequences used for this difference spectrum method are exemplified in FIGS. 4A and 4B. A pulse sequence of 90xc2x0-180xc2x0 pulses shown in FIG. 4A enables a spin echo signal to be acquired. An echo time TE in this acquisition is set to xc2xdJHH, i.e., 68 ms. In addition, jump and return pulses are used as the 180xc2x0 pulse. The jump and return pulses are composed of two 90xc2x0 pulses so as to form complex pulses radiated to GABAs other than the GABA-3 by setting a center frequency between the 90xc2x0 pulses to the GABA-3, that is, 1.91 ppm. Additionally, the jump and return pulses can be composed so as to function as almost a 180xc2x0 pulse toward the GABA-4, that is, 3.01 ppm within an object to be observed.
As shown in FIG. 4B, a pulse sequence formed by adding xe2x80x9cdelays alternating with nutations for tailored excitation (DANTE) pulsesxe2x80x9d to the foregoing pulse sequence can be used for acquiring spin echo signals. The DANTE pulses are narrower in bandwidth and their carrier frequencies are determined so that the DANTE pulses are radiated to 1.91 ppm, that is, the GABA-3.
The two hydrogen nuclei 1H of the GABA-4 are not equivalent to each other in terms of their magnetism, and JHH-coupled to the two hydrogen nuclei 1H of the GABA-3. As a result, the GABA-4 represents four split peaks, but the central two peaks are overlapped one on another in vivo. The three split peaks are thus observed, in which a frequency difference between the outside two peaks corresponds to double the JHH.
When executing the pulse sequence shown in FIG. 4A toward the GABA, a spectrum pattern shown in FIG. 5A is obtained. Further, when executing the pulse sequence shown in FIG. 4B, a spectrum pattern shown in FIG. 5B is obtained, because the GABA-3 is inverted. Thus, a difference is calculated between the spectra shown in both FIGS. 4A and 4B, resulting in that only the outside two peaks of the spectrum of the GABA-4 are obtained (refer to FIG. 5C). It is therefore possible that a signal of Cr (3 ppm) that has a 1H chemical shift approximately equal to the GABA-4 (has a hydrogen nucleus 1H of which chemical shift is 3.01 ppm) can be removed.
Another pulse sequence is shown in FIG. 6, which has been devised on the basis of the difference spectrum method that is able to edit a signal of the GABA-4 detected from a spatial three-dimensional localized region (refer to xe2x80x9cO. M. Weber et al., Proceeding of International Society of Magnetic Resonance in Medicine, p.522, 1995xe2x80x9d).
However, in the case that the above techniques are used, it is significant that the system is stable in both performing a sequence with no DANTE pulse and performing another sequence with DANTE pulses. Because the spectrum peak of Cr is about twenty times as large as that of the GABA in intensity, unstable factors of the system, such as slight fluctuations in the intensify of an RF magnetic pulse, make it difficult to edit the signal of GABA-4.
On the other hand, differently from the above method, another editing technique of the GABA-4, which uses multiple-quantum coherences, has been proposed. Since there are JHH-couplings in the GABA-3 and -4, it is possible to create the multiple-quantum coherences. A pulse sequence for such method is depicted in FIG. 7. In this pulse sequence, the first three RF pulses consisting of a 90xc2x0 pulse, a 180xc2x0 pulse, and a 90xc2x0 pulse are applied to create multiple-quantum coherences of the GABA-3 and -4. FIG. 7 also shows coherence-transfer pathways to be selected during the performance of this pulse sequence. As shown by the pulse sequence in FIG. 7, it is required that time periods between the pulses be set to 1/(8JHH) and the phases of the first and third 90xc2x0 pulses be set to x. The multiple-quantum coherences generated by the above three pulses are then subject to a further 90xc2x0 pulse to be applied in succession, so that the coherences are formed into the single quantum-coherence, which is observable. The duration of the multiple-quantum coherences, that is, a period between the third and fourth 90xc2x0 pulses is expressed by tmq that means multiple-quantum coherences.
During the period tmq in the pulse sequence, the 1H chemical shift is evolved. For re-imaging the hydrogen nuclei 1H of the evolved chemical shift, another 180xc2x0 pulse may be applied at the center of the period of tmq. A pulse sequence including such 180xc2x0 pulse is shown in FIG. 8 (refer to xe2x80x9cJ. R. Keltner et. Al., Magn. Reson. Med., vol. 37, pp.366-371, 1997xe2x80x9d). The pulse sequence in FIG. 8 additionally uses the forgoing 90 xc2x0xe2x88x9290xc2x0 pulses, that is, jump and return pulses not to excite a water signal. When using the methods with the multiple-quantum coherences, the water signal can be suppressed by a coherence selective gradient pulse as well as a chemical shift selective (CHESS) pulse. The foregoing pulse sequences permit multiple-quantum coherences, that is, zero-quantum and double-quantum coherences to be generated during the tmq period. The orders of the coherences are 0 (zero), +2, and xe2x88x922. A gradient pulse applied during the tmq period will not dephase the zero-quantum coherence, but will dephase the double-quantum coherences to phases of xe2x80x9cxc2x12xcex31H∫tg0G1dt,xe2x80x9d wherein xcex3H is a gyromagnetic ratio, G is the intensity of the gradient pulse, and tg is an application time of the gradient pulse.
After the multiple-quantum coherences, there is provided a period for a single-quantum coherence. The coherence with the order of xe2x80x9cxe2x88x921,xe2x80x9d which can be detected by quadrature phase detection, has a phase of xe2x80x9cxe2x88x92xcex31H∫tg0G2dt.xe2x80x9d Accordingly, when a radio of G1:G2 is for example set to 1:2, coherence-transfer pathways of xe2x80x9c2 to xe2x88x921xe2x80x9d can be chosen, thus a signal from water (water signal) and a signal from Cr (Cr signal) being suppressed. Differently from this way of suppressing the water signal, the suppression method that makes use of the CHESS pulse has a performance depending on a frequency distribution, that is, magnetic non-uniformity or fluctuations in frequency. However, the method based on the foregoing coherence selective gradient pulses uses the coherence-transfer pathways of xe2x80x9c2 to xe2x88x921.xe2x80x9d As a result, although the sensitivity reduces down to the half obtained by the CHESS pulse method, the method that uses the coherence selective gradient pulses has still an advantage that it does not depend on the magnetic non-uniformity, thus being robust. This feature is significant for signal detection from an organism.
The GABA editing method based on the multiple-quantum coherences has the advantage descried above. However, in the case of this method, to create the multiple-quantum coherences requires that phases of the first and second 90xc2x0 pulses be adjusted in a critical manner. A poor adjustment of those phases may affect sensitivity in the acquisition of signals. During the performance of the pulse sequence, gradient pulses are applied to define a region to be localized. Coupling between the gradient pulses and the coil of a static magnet causes a phenomenon, called B0 shifts, when the gradient pulses are applied, thus leading deviations in the phase. This reduces the sensitivity, and requires that RF signals be adjusted in the phases when the gradient pulses are applied.
Further, since the foregoing method based on the multiple-quantum coherences additionally selects the nuclei 1H of JHH-coupled metabolites other than GABA, there are provided peaks other than a desired peak in the spectrum, thus giving complication to the spectrum. For example, FIG. 6 shown in the paper xe2x80x9cJ. R. Keltneretal., Magn. Reson. Med., vol. 37, pp. 366-371 (1997),xe2x80x9d which proposes a GABA editing method on the basis the multiple-quantum coherences, provides a spectrum that bristles with the peaks of NAA, glutamic acid, and glutamine (both of the glutamate and the glutamine are impossible to separate in the spectrum, so shown by a reference xe2x80x9cGLxxe2x80x9d). This involves a post processing operation to extract only the peak of the GABA, making the operations cumbersome.
Another pulse sequence is shown in FIG. 9, in which non-selective excitation pulses are used for generating multiple-quantum transfers, then succeeding RF pulses applied after the tmq period are in charge of localized excitation (refer to xe2x80x9cJ. Shen et al., Magn. Reson. Med., vol. 41, pp.35-42, 1999xe2x80x9d). In this pulse sequence, three non-selective excitation pulses generate the multiple-quantum coherences, and then a frequency-selective radiation 180xc2x0 pulse (sel 180xc2x0) directed to the GABA-4 is applied to invert only the GABA-4. A frequency-selective radiation 90xc2x0 pulse (sel 90xc2x0) is then applied to the GABA-3 in order to generate the single-quantum coherence. Two slice-selective RF pulses are then used to edit only the GABA-4. When this sequence is used to carry out a spatial three-dimensional localized excitation, it is required, as explained above, that the three RF pulses be applied to obtain functions of slice-selective RF pulses after the tmq period. That is, at least eight RF pulses should be applied. However, the application of a large number of RF pulses will lead to a problem that a signal loss is caused more easily due to errors in flip angles or RF distributions.
Still another editing method that uses the multiple-quantum coherences has been proposed by xe2x80x9cQ. HE et al., J. Magn. Reson. B. vol. 106, pp.203-211 (1995).xe2x80x9d A pulse sequence according to this proposal is directed to detecting spectroscopy of lactate, which is outlined in FIG. 10. As shown therein, the pulse sequence employs a frequency selective radiation pulse applied first to CH3 (lipid) of a molecule of the lactate. A second frequency selective radiation pulse is then applied to the 1H of CH JHH-coupled with the CH3. This application is then followed by a 180xc2x0 RF pulse applied in a non-selective manner, then a third frequency selective radiation pulse is again applied to the 1H of the CH to acquire an echo signal.
However, in the pulse sequence shown in FIG. 10, the first-applied excitation pulse is composed of a frequency selective radiation pulse directed to the CH3. Therefore, the frequency of the frequency selective radiation pulse should be strictly equal to the resonance frequency of the CH3, which involves cumbersome operations to adjust the frequency. Further, because it is required that the bandwidth of the first excitation pulse be narrow, its RF pulse length (the length of a pulse in the time axis direction) becomes necessarily longer than that of a wideband pulse. Hence, the strength of a slice gradient pulse applied concurrently with the first excitation pulse should be lowered compared to that for a wideband pulse. The pulse sequence shown in FIG. 10 requires that the static field be higher in its non-uniformity.
An object of the present invention is therefore to provide a technique of acquiring an echo from JHH-coupled 1H based on a magnetic resonance phenomenon, the technique being robust to unstable factors of a system, eliminating the necessity of adjusting phases of radio-frequency magnetic pulses to be applied, being able to obtain a spectrum shown in a simplified form, and having higher resistance to signal loss due to errors in flip angles and/or radio-frequency magnetic distributions.
In order to realize the above object, the present invention provides, as one category, a method of acquiring a magnetic resonance signal. The acquisition method is able to acquire the magnetic resonance signal from a nucleus 1H involving a homonuclear spin-spin coupling exerted between nuclei 1H by applying to an object placed in a static magnetic field, radio-frequency magnetic pulses and gradient magnetic pulses in predetermined procedures on the basis of a resonance frequency of hydrogen nuclei 1H. This acquisition method is provided in three fundamental modes.
A first mode is provided by the acquisition method comprising the steps of applying to the object a first radio-frequency magnetic pulse to excite the nuclei 1H of a plurality of compounds; applying, after applying the first radio-frequency magnetic pulse, to the object a first frequency-selective radiation pulse to excite a specific nucleus 1H coupled to a desired nucleus 1H among the nuclei 1H of the plurality of compounds through the homonuclear spin-spin coupling; applying, after applying the first frequency-selective radiation pulse, to the object a second radio-frequency magnetic pulse; applying, after applying the second radio-frequency magnetic pulse, to the object a second frequency-selective radiation pulse to excite the specific nucleus 1H; and acquiring, after applying the second frequency-selective radiation pulse, the magnetic resonance signal of the desired nucleus 1H.
A second mode is provided by the acquisition method comprising the steps of applying to the object a first radio-frequency magnetic pulse and a second radio-frequency magnetic pulse in sequence; applying, after applying the first and second radio-frequency magnetic pulses, to the object a first frequency-selective radiation pulse to excite a specific nucleus 1H coupled to a desired nucleus 1H through the homonuclear spin-spin coupling; applying, after applying the first frequency-selective radiation pulse, to the object a third radio-frequency magnetic pulse; applying, after applying the third radio-frequency magnetic pulse, to the object a second frequency-selective radiation pulse to excite the specific nucleus 1H; and acquiring, after applying the second frequency-selective radiation pulse, the magnetic resonance signal of the desired nucleus 1H.
A third mode is provided by the acquisition method comprising the steps of applying to the object a first radio-frequency magnetic pulse; applying, after applying the first radio-frequency magnetic pulse, to the object a first frequency-selective radiation pulse to excite a specific nucleus 1H coupled to a desired nucleus 1H through the homonuclear spin-spin coupling; applying, after applying the first frequency-selective radiation pulse, to the object a second radio-frequency magnetic pulse; applying, after applying the second radio-frequency magnetic pulse, to the object a second frequency-selective radiation pulse to excite the specific nucleus 1H; applying, after applying the second frequency-selective radiation pulse, to the object a third radio-frequency magnetic pulse; and acquiring, after applying the third frequency-selective radiation pulse, the magnetic resonance signal of the desired nucleus 1H.
In the above first to third modes, in replay to the application of the first frequency-selective radiation pulse, multiple-quantum coherences are generated. Then, in reply to the application of the second frequency-selective radiation pulse (in the case of the first and second modes) or the third radio-frequency magnetic pulse (in the case of the third mode), the single-quantum coherence is generated. This makes it possible to acquire a magnetic resonance signal of a desired nucleus 1H. Hence only a desired peak for a desired hydrogen nucleus 1H can be obtained in a spectrum. Further, because sensitivity in acquiring a signal according to this signal acquisition technique does not depend on phases of radio-frequency magnetic pulses, it is unnecessary to adjust such phases. Still further, the number of radio-frequency magnetic pulses to be applied for acquiring a magnetic resonance signal is four or five, which is a necessary minimum number. The system is therefore robust to errors in flip angles given to the pulses and signal loss resulted from radio-frequency magnetic distributions. Signal loss will not therefore be caused easily due to such factors.
In the configurations according to the above three modes, the application of the frequency-selective radiation pulses and radio-frequency magnetic pulses may be accompanied by the application of plural gradient pulses, and those plural gradient pulses may be determined to maintain a predetermined ratio of their intensities. By way of example, for the above first mode, it is preferred that a first gradient pulse is applied during a period of time lasting from a time at which the application of the first frequency-selective radiation pulse finishes to a further time at which the application of the second radio-frequency magnetic pulse starts, a second gradient pulse is applied during a period of time lasting from a time at which the application of the second radio-frequency magnetic pulse finishes to a further time at which the application of the second frequency-selective radiation pulse, and a third gradient pulse is applied during a period of time lasting from a time at which the application of the second frequency-selective radiation pulse finishes to a further time at which the acquisition of the magnetic resonance signal starts, wherein, when a time integral value of an intensity of the first gradient pulse is expressed by G1, a time integral value of an intensity of the second gradient pulse is expressed by G2, and a time integral value of an intensity of the third gradient pulse is expressed by G3, the time integral values G1, G2 and G3 are determined to meet a condition of 2G1xe2x88x922G2xe2x88x92G3=0. This allows the gradient pulses to select desired coherence-transfer pathways, which makes the system robust highly to various unstable factors of the system, such as fluctuations in intensity of the radio-frequency magnetic pulses.
Furthermore, in the configurations according to the above three modes, it is also preferable that, of the plural radio-frequency magnetic pulses (for example, in the case of the first mode, the first and second radio-frequency magnetic pulses), at least one magnetic pulse is set as a slice-selective pulse applied concurrently with a slice gradient pulse. By employing this configuration, a magnetic resonance signal can be acquired from a one-dimensionally, two-dimensionally, or three-dimensionally localized region of an object to be examined.
Moreover, the foregoing three modes can be configured such that the hydrogen nuclei 1H included in xcex3-aminobutyric acid (GABA) present within the object and the desired nucleus 1H composes a GABA-4 coupled to a GABA-3 through the homonuclear spin-spin coupling.
On the other hand, as another category of the present invention, there are provided magnetic resonance systems capable of performing the acquisition methods based on the foregoing first to third modes. These systems are also able to provide a variety of advantages similarly to the above acquisition methods.
According to the present invention, there is also provided a recording medium in which a computer-readable program is stored which has the capability of performing the acquisition method according to the second mode.